ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Clinical Infectious Diseases
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1663857
This article is part of the Research TopicExploring Clinical Application Scenarios of Metagenomic Next-Generation Sequencing for Pathogen DiagnosisView all 9 articles
Utilization of Cell-Free DNA Metagenomic Analysis for Early Detection and Microbial Identification in Prosthetic Joint Infections: A Prospective Cohort Study in Korea
Provisionally accepted
- Yonsei University College of Medicine,, Seoul, Republic of Korea
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Background Prosthetic joint infection (PJI) is a severe complication of hip or knee arthroplasty, often necessitating invasive intervention and posing a high risk of adverse outcomes. Early diagnosis and tailored antibiotic therapy are critical for the effective management of PJI. This study evaluated the utility of cell-free deoxyribonucleic acid (cfDNA) extracted from synovial fluid to diagnose PJI and identify the causative pathogens. Methods This prospective, single-center study included a PJI group consisting of patients with confirmed infections based on the European Bone and Joint Infection Society criteria and a non-PJI group comprising patients without suspected PJIs who underwent joint surgery 2 or aspiration. Synovial fluid samples were collected from all patients, and various culture methods, including conventional synovial fluid, sonication, and tissue and blood cultures, were applied along with cfDNA analysis. Results A total of 35 patients were included, with 20 diagnosed with PJI and 15 classified as non-PJI. The median cfDNA concentration in synovial fluid was significantly higher in the PJI group (4.560 ng/μl, interquartile range (IQR) [3.320–6.348]) compared with the non-PJI group (0.028 ng/μl, IQR [0.009–0.273]) (p < 0.001). The Youden index identified a cfDNA concentration ≥ 1.59 ng/μl as strong likelihood of PJI. Culture positivity rates in the PJI group were as follows: synovial culture (10/20, 50.0%), sonication culture (8/9, 88.9%), tissue culture (2/8, 25.0%), and blood culture (2/12, 16.7%). The bacterial detection rate of cfDNA was 65.0% (13/20). Conclusion cfDNA concentration was significantly higher in the PJI group, with synovial cultures showing substantial agreement. Additionally, cfDNA sequencing detected pathogens in patients who had received prior antibiotic therapy and identified multiple pathogens in polymicrobial infections. These findings highlight cfDNA analysis as a valuable diagnostic tool for PJI, with the potential to enhance current diagnostic approaches.
Keywords: cell-free deoxyribonucleic acid, Metagenomics, Prosthetic joint infection, Synovial Fluid, diagnostics
Received: 11 Jul 2025; Accepted: 01 Oct 2025.
Copyright: © 2025 Lee, Lee, Won, Lee, Park, Shin and Jeong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Saeam Shin, saeam0304@yuhs.ac
Su Jin Jeong, jsj@yuhs.ac
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